
The Next Thing You Smell Could Ruin Your Life
After my birth, my mother became allergic to the world. That's the only way I knew how to put it. So many things could set her off: new carpeting, air fresheners, plastic off-gassing, diesel. Perfumes were among the worst offenders. On top of that, she developed terrible food allergies. The sound of her sniffling became the chorus of my childhood. Some days she couldn't get out of bed. I'd peek into her darkened room and see her face pinched in discomfort.
Her joints ached, her head swam. Doctors suggested that maybe she was depressed or anxious. 'Well, you'd be anxious too if you couldn't lick an envelope, couldn't pick up your daughter in a car,' she'd reply. She tried allergists, got nowhere. Finally, she found her way to holistic health, whose practitioners told her she had something called multiple chemical sensitivity.
As long as people have complained that man-made stuff in their environment causes health problems—migraines and asthma, exhaustion and mood swings—the medical establishment has largely dismissed them. The American Medical Association, World Health Organization, and the American Academy of Asthma, Allergy & Immunology don't recognize chemical sensitivity as a diagnosis. If they talk about it at all, they tend to dismiss it as psychosomatic, a malady of the neurotic and health-obsessed. Why, these authorities wondered, would people react to minute traces of a huge array of chemicals? And why couldn't they ever seem to get better?
This isn't some trivial affliction. Roughly a quarter of American adults report some form of chemical sensitivity; it lives alongside chronic pain and fibromyalgia as both evidently real and resistant to mainstream diagnosis or treatment. My mom tried a thousand things—elimination diets, antihistamines, lymphatic massage, antidepressants, acupuncture, red light therapy, saunas, heavy-metal detoxes. Sometimes her symptoms eased, but she never got better. Her illness ruled our lives, dictating what products we bought, what food we ate, where we traveled. I felt there had to be an answer for why this was happening. It didn't take me long to learn that, if there was one, it'd come from a figure as unassuming as she is provocative: the scientist Claudia Miller.
On a warm Texas afternoon, Miller and her affable husband, Bob, lead me through the San Antonio Botanical Garden. A monarch flits by. 'I've noticed so many fewer butterflies, so many fewer birds, even the last couple of years,' Miller observes. Her raspy voice comes out so quietly that, at times, my recording device fails to pick it up. People are perpetually leaning in close or asking her to repeat herself. At 78, Miller typically uses a cane, but Bob gets the walker out of the car so she can cover more distance. She wears her silver hair in a low side ponytail, fixed in place with a scrunchie.
With her wide, thin-rimmed glasses, Miller disappears into the scenery, but she's a particularly visible presence in her field. Now a professor emeritus at the University of Texas Health Science Center at San Antonio, Miller has held several federal appointments, chaired National Institutes of Health meetings, testified before Congress, consulted for the Environmental Protection Agency, authored dozens of papers, and worked with the Canadian, German, Japanese, and Swedish governments. In all this, she has tried to make sense of and raise awareness for chemical intolerance. One patient advocate I interviewed called her 'Saint Claudia' for her commitment to overlooked and misunderstood patients. Kristina Baehr, an attorney who defends victims of toxic exposures, told me, 'To have experts like Dr. Miller tell them you're not crazy, this is very real, is very life-giving to people. She's able to validate their experience with facts, with science.'
One such fact, Miller explains, is this: Over the past century, the United States has undergone a chemical revolution. 'Fossil fuels, coal, oil, natural gas, their combustion products, and then their synthetic chemical derivatives are mostly new since World War II,' she says. 'Plasticizers, forever chemicals, you name it: These are all foreign chemicals.' They're everywhere you look, in homes and offices, parks and schools. They're also, Miller believes, making people very sick.
In 1997, Miller proposed a career-defining theory of how people succumb to this condition. It came with a technical-sounding name, toxicant-induced loss of tolerance, and a convenient acronym, TILT. You can lose tolerance after one severe exposure, Miller says, or after a series of smaller exposures over time. In either case, a switch is flipped: Suddenly, people are triggered by even tiny amounts of everyday substances—cigarette smoke, antibiotics, gas from their stoves—that never bothered them before. These people become, in a word, TILT-ed. It's not unlike developing an allergy, when the body labels a substance as dangerous and then reacts accordingly.
In 1999, Miller and her colleagues designed the Quick Environmental Exposure and Sensitivity Inventory, or QEESI (pronounced 'queasy'), a survey to help doctors and researchers identify chemically intolerant patients. I've seen the QEESI cited in papers from 18 countries, but to date, most physicians still don't know much about it. 'It's very frustrating to try to get these ideas across,' Miller says. The major problem is that, assuming TILT accurately describes the process of becoming chemically intolerant, we don't know what biological changes occur inside the sensitized body, why so many symptoms crop up, or why one exposed person gets sick while others seem to walk away unscathed. But Miller thinks she's closer than ever to an answer.
At the botanical garden, we approach an orchid exhibit. Sticky heat engulfs us as we enter. Orchids of varying shapes and colors fill the greenhouse, including one with spindly chartreuse petals. 'What do you call this?' Miller asks. My plant-ID app comes up empty. So it goes, too, for chemically intolerant patients: The condition defies easy observation. 'The world becomes like a torture chamber, and then nobody believes you,' Miller says. 'That's the worst part.' After falling ill, some people become hermits out of fear of exposure, abandoning their friends and family to live in remote areas. For others, nothing can keep them from spinning out of control. My mother knew someone who tried to escape her triggers by moving to the country in a trailer. Eventually, even that became unmanageable, and the woman shot herself in the head.
Imagine feeling incredibly sick every time you encounter a cloud of cologne or fresh paint, then being told you're making it up. I thought about my mom. Sometimes, catering to her needs could feel exhausting. But what must that have been like for her? The thing was, I never doubted her condition—especially after what happened on one bad day.
A crucial textbook from Miller's library. Photograph: Amber Gomez
Masks can help protect TILT-ed patients. Photograph: Amber Gomez
It's time to tell you the worst thing I have ever done to another person. When I was 10, my parents and I attended a family reunion. The trip was difficult. We fought nonstop. Everyone cried. The photographer hired to capture a family portrait accidentally exposed the film to light, and it was just as well. If we could have wiped the whole week from our minds, we would have.
During that ill-fated trip, my aunt gifted me a set of scented lip balms. My mom offered her a tight smile but, once we were alone, told me to toss them out. Instead, I hid them and, soon, weaponized them. After yet another argument, I sneaked into my mom's room, peeled back her pillow case, and smeared the lip balms directly onto her pillow. Later that night, as she tried to sleep, she kept waking up, sicker and sicker, her head pounding. Finally, her nose helped her uncover what I'd done. She found the telltale smudges. The next day, my dad told me how she'd sobbed and howled, 'Why would she do this to me?'
It remains, for me, a source of immense guilt. Later, I realized it was also the crumb of proof I needed. This was not all in my mother's head.
I'm at Miller's condo across the street from the UT Health Science Center, with Miller and two of her collaborators. Her dining room table is lined with household products—a votive candle, a box of matches, body lotion, scented dish detergent. Beside them are chunky gadgets that look like something out of Ghostbusters . These are particulate monitors, which measure down to parts per billion. They need to be hypersensitive, because products like the ones on the table expel tiny molecules, and people with chemical intolerance seem to react to even minuscule doses. It's akin to someone having an allergic reaction to a bag of peanuts opened on the other end of the airplane. One of her collaborators strikes a single match in front of a sensor. The number on the screen rockets from 0 to almost 500,000 parts per billion. It's not always about what the nose can detect—though, in this case, sulfur dioxide fills the room.
Last year, Miller's team published research on house calls for nearly 40 people with chemical intolerance. They measured indoor pollution from products like these, as well as other irritants like dust and mold, and performed blood tests for allergies. Then they recommended tossing out scented candles or moving cans of gasoline from an attached garage to a separate storage unit, and gifted the subjects natural cleaning products. They retested the homes several more times over the course of the year. As the indoor pollution decreased, the subjects' symptoms improved.
For years, research like this convinced Miller that there was, indeed, something very wrong with her patients. But, again, that pesky mechanism for disease eluded her. Then she learned more about mast cells.
Mast cells are a type of white blood cell that exists in nearly every tissue, including the skin, airways, and gastro-intestinal tract. When they detect something harmful, they can release hundreds of mediators, including histamine, substances that create symptoms like hives or swelling during anaphylactic shock. If the cells become overreactive, releasing too many mediators at the wrong time, a person can end up flushed, dizzy, wheezy, or exhausted. This is called mast cell activation syndrome, or MCAS. When Miller came across a book on the subject by Lawrence Afrin, a hematologist and mast cell disease researcher based in New York, she thought it sounded a lot like chemical intolerance. She called him. Many of his MCAS patients, it turned out, were sensitive to fragrances and medications.
In 2021, Miller published what she considers her second eureka moment: a paper, coauthored with Afrin and others, that explains a potential link between TILT and MCAS. The team surveyed MCAS patients and found that those who scored high on MCAS questionnaires scored high on the QEESI. These patient groups also had nearly identical symptom patterns. Had Miller's patients had mast cell activation syndrome this whole time? MCAS is a tricky disease to diagnose and treat, but it was something. An answer for the scientific community. An answer for her patients. And an answer for herself.
Because that's the other part of this story, the part Miller hasn't been comfortable talking about until now: She, the condition's leading researcher, suffers from chemical intolerance too.
Miller has difficulty searching her memory about her past. Exact years don't come back to her, her retellings wander. Attribute it to age or brain fog or both. Still, over hours of conversations and dozens of emails, her story came together.
Born in Milwaukee as the only child of a patent attorney and a teacher, Miller was drawn to science from a young age. After earning her BA in molecular biology from the University of Wisconsin–Madison and her master's in environmental health from UC Berkeley, she spent several years in Chicago working for OSHA and the United Steelworkers union as an industrial hygienist, touring steel mills, coke ovens, and smelters to monitor worker health and safety. She began seeing snapshots of the condition that would define her career. Once, she was called to meet with women who soldered in an electronics plant. 'They had some outbreaks of so-called mass psychogenic illness,' Miller said. 'A manager brought one of these women into the office. He actually started soldering right in front of us and she starts to have her symptoms, sneezing or whatever.' To the manager, this proved that it was psychological—why should his worker be impacted if he and Miller were not? Miller suspected something else was at play, though she couldn't put her finger on what.
Imagine feeling incredibly sick every time you encounter a cloud of cologne or fresh paint, then being told you're making it up.
She met Bob, a fellow industrial hygienist, through OSHA. By 1977, the Millers were newlyweds living in an old home in a verdant area of Lake Forest. They loved gardening and the foxes that visited the nearby pond. But the house had wasps and spiders. Miller did her research and found an EPA-approved pesticide for indoor use, which an exterminator sprayed on her floorboards and eaves. 'That changed our whole lives,' Miller said.
Immediately, Miller was walloped with fatigue and mired in confusion. Her husband felt OK, so they decided to still go on their honeymoon in New Orleans. They left their two-month-old Burmese kitten with Miller's parents. On the trip, they got a call. 'This cat looks kind of droopy,' Miller remembers her parents saying. The next day, the kitten died.
Miller suspected that the pesticide had affected both her and her cat, but she couldn't figure out how to get well. Then she was referred to Theron Randolph, an infamous allergist who broke ranks with the medical establishment after working with chemically sensitive patients. Other allergists stood by the idea that 'the dose makes the poison'—basically, that any substance, even water or oxygen, can be harmful in excess, but trace chemicals shouldn't sicken patients. Randolph disagreed, saying that small doses mattered and that bodies could accumulate toxic burdens over time. He also mounted a campaign against corn, believing it caused inflammation and brain fog. For this and other work, he was ousted from his faculty position at Northwestern University Medical School. By the time Miller met him, he'd become a lightning rod for criticism from peers, who accused him of relying too heavily on patient testimonials and unconventional testing methods.
'The world becomes like a torture chamber, and then nobody believes you,' Miller says. 'That's the worst part.' Photograph: Amber Gomez
Unaware of this controversy and desperate to regain her health, she checked herself in for three weeks at one of the 'environmental medical units' Randolph had established in the wing of a hospital. In Randolph's opinion, Miller had to clear out her body before she could determine what was triggering her illness. Miller was confined to a unit with three other sick women, all with different symptoms. The rooms were outfitted with materials that wouldn't outgas—ceramic-lined floors and walls, metal furniture. The hospital filtered in fresh air, with air-locked entrances. No disinfectants or fragrances were allowed inside. The program began with a nearly weeklong fast. By her third day, Miller felt incredible: 'Your head is clear, you can remember things.'
It piqued Miller's scientific curiosity. Randolph spent a few minutes with patients each day, and Miller flooded him with questions. Eventually, she delayed his rounds so much that he asked if she wanted to come to his staff meetings. Soon, she became a collaborator of sorts and, in the summer of 1979, presented at an NIH meeting on mass psychogenic illness. She discussed case studies of patients who fell ill after specific chemical exposures. This wasn't hysteria, she argued; there was cause and effect. Afterward, she said, attendees lined up at the microphone to challenge her—a glimpse at the pushback that would shadow her for years.
Randolph suggested Miller attend medical school. If she had any hope of breaking through to the establishment, she recalls him saying, 'you've got to learn everything they know.' But there were a few problems. The stay at the environmental medical unit only temporarily improved her health. When she returned to her Chicago home, she became sick again. So she and her husband moved to Texas, where Miller became a medical student at UT. 'If I had revealed my own intolerances, I would never have been accepted,' she told me. She pretended she was merely interested in allergy and immunology. All the while, she privately struggled. If a patient came in reeking of cigarette smoke, she might be sidelined with dizziness. By that point, most meals made her sick too. 'Her main food was chocolate,' Bob jokes. Sometimes, she would fast before her exams to try to regain some of the clarity she felt in Randolph's care.
After earning her degree, Miller began her 'real' work in earnest. She was appointed to the National Advisory Committee on Occupational Safety and Health, where she met Nicholas Ashford, an environmental policy lawyer and MIT professor. When the state of New Jersey tapped Ashford to study chemical sensitivity, he tapped Miller as his coauthor. So began a career-long collaboration. They published their New Jersey report in 1989, followed by a seminal book, Chemical Exposure: Low Levels and High Stakes , in 1991.
'I'm not saying I deserve a Nobel Prize,' Claudia Miller tells me. 'But it's at that level.' Her husband chimes in: 'Basically a new theory of disease.'
Miller confided in Ashford about her condition, but he advised her to continue keeping it a secret. 'You don't want to cloud the good science that you're doing,' she recalls him telling her. She obliged. The Department of Veterans Affairs contracted her to study Gulf War veterans exposed to chemical weapons who came home and could no longer tolerate common smells like WD-40 or a girlfriend's nail polish. She corresponded with congressman Bernie Sanders for years to try to get the government to build environmental medical units. She met with some of the 100 EPA workers who, after their department installed latex-backed carpet, complained about blurred vision and chest pain. She testified before the Food and Drug Administration about patients who'd received breast implants and suddenly couldn't drink alcohol or caffeine. All the while, she suffered her illness in silence. Then, some 40-plus years after her pesticide exposure, Miller found her way to mast cells—and, with that, the confidence to finally come forward.
When Miller and I are alone in her condo, she shows me some of her art. In her office, we stand before two illustrations depicting Don Quixote and his famously misguided quest to become a hero. The first piece shows the aftermath of when he mistook windmills for giants and attacked them. He and his horse lay on the ground, battered, with their legs in the air. 'He's tilting at windmills,' she says. 'That's what I feel like I'm doing.' I understand the play on words, but I don't say what I'm thinking: that Don Quixote, in his deep obsession, imagined enemies where there were none.
Miller comes across as single—almost monolithically—minded. Her preferred talking points include Elon Musk, whom she brought up to me by phone, in person, over emails. Her research has found that those with high chemical-intolerance scores are 5.7 times more likely to have a child with autism and 2.1 times more likely to have one with ADHD. (Sample size of one here, but I, a child of a chemically intolerant woman, have ADHD.) During my visit, Miller handed me a copy of Musk's mother's memoir, which has one line mentioning that she painted her husband's plane while pregnant with Elon. Miller speculates that this exposure may have influenced his neurological development. (In 2021, Musk publicly stated he has Asperger's, an autism spectrum disorder.) An article about this 'could crack open the field,' as she put it. Perhaps, she wondered aloud, he might even build Randolph-style environmental medical units. Unprompted, Miller wrote me an email one day that read, in its entirety: 'When I was an eight-year-old girl, living in Milwaukee, I never imagined I would become a doctor and diagnose the richest man in the world.'
Another sticking point: terminology. She reviles the name 'multiple chemical sensitivity,' which she sees as a stigmatizing and imprecise label. On its face, the term does not acknowledge patients TILT-ed by, say, mold exposure, a common initiating event. It's also dismissed in lawsuits under the Daubert and Frye standards, which let judges block expert testimony on conditions lacking wide scientific acceptance. Multiple chemical sensitivity may describe how many patients feel, Miller says, but it's a diagnosis without a clear medical explanation. Chemical intolerance is a more accurate term, she argues, and TILT is that missing medical explanation—and that should be the focus of research. This has become one of the issues at the core of her fracturing with the chemical intolerance community. The other, no surprise, is money.
Funding is scarce in this niche and polarizing area. At UT, Miller was able to piece together government grants for some of her work, but she also routinely invested her own money. In 2013, everything changed. An heiress named Marilyn Brachman Hoffman died, leaving more than $50 million to a foundation in her name. Hoffman was a fellow sufferer of chemical intolerance and, throughout her life, corresponded with a handful of scientists, including Miller. In her personal will and trust, Hoffman also gifted $5 million to Harvard for research on 'toxicant-induced loss of tolerance.' She noted that Miller should join the advisory committee. Indeed, Miller did so for a year as a part-time senior scientist. Then, in 2015, she and her colleagues set up the Hoffman Program for Chemical Intolerance out of UT Health San Antonio, with funding from the foundation.
The Harvard group never produced any research specifically on TILT (though they did study indoor air pollution, among other things). And, in recent years, the foundation has turned its attention elsewhere—namely, to research about multiple chemical sensitivity. Miller has felt left out in the cold. Hoffman specifically mentioned TILT in her will, not multiple chemical sensitivity. The executor of Hoffman's will, an estate lawyer who became president of the foundation, worked for a large law firm that had defended pesticide and petrochemical companies. Was the foundation funding multiple chemical sensitivity instead of TILT, Miller wondered, as a way to delegitimize patients? (When asked for comment, the foundation said it's still open to funding projects related to TILT but added: 'The fact that we do not solely use the term TILT, which is almost exclusively associated with Claudia Miller's work, may be a problem for her, but it is not a conspiracy to hurt people.')
Miller's distrust is, in many ways, understandable. Her work butts up against the interests of huge companies and powerful people; she has spent her career watching her patients get dismissed. In an email to her coauthor Ashford, she mentioned that members of the foundation board considered her difficult: 'Yes I am difficult—I am precise about my science and will not tolerate any tampering with the truth or any attempts to derail my research.'
I witnessed a piece of the drama myself when I attended an international conference on chemical intolerance, held over Zoom. Though there was one talk specifically on TILT, most of the presenters used the term multiple chemical sensitivity. After a Canadian physician concluded one session, the hosts fielded an audience question. Miller's coauthor, Ashford, crackled to life. He urged the conference attendees to read his work with Miller and Afrin on mast cells. 'We think we have cracked the code on chemical sensitivity,' he said. He then pivoted to criticizing the conference. 'Without clarifying what's causing or priming the patient, we're not going to get anywhere,' he said. 'And I'm very disappointed to see this isn't emphasized.' He blinked. Silence hung in the digital air. Finally, one of the cohosts diplomatically thanked Ashford for 'that intervention.' (Later, Miller told me that she'd been invited to present but had refused because of the focus on multiple chemical sensitivity: 'I just couldn't stomach it.')
Whether you consider it steadfastness or stubbornness or something else, Miller's approach has come at the cost of her relationships. Many people I reached out to opted not to speak with me. I began to get similar reactions when I asked sources about her work. They didn't want to criticize her: She has dedicated her life to this understudied condition, but …
Her biggest barrier is that TILT has yet to be proven. 'Where the evidence is not strong, you very often find strongly held opinions,' Jonathan Samet, former dean of the Colorado School of Public Health and member of the Hoffman Foundation's scientific advisory board, told me. When I asked him specifically about TILT, he took a deep breath. He noted that few people have been so serious about this issue as Miller. 'I don't want to go into a critique—I mean, I think it's very reasonable to make hypotheses,' he said. 'I think the more challenging question is: What is the research that actually tests the hypothesis?'
Supposing that TILT is real, mast cells remain difficult territory. There's no definitive cause of MCAS, only more (yes) hypotheses. Questions remain: Could TILT cause MCAS, or do patients have preexisting MCAS, which is exacerbated during exposure events? Are these conditions, in fact, related at all? 'This is the danger of mistaking association for causation,' Afrin says. 'Just because two things are associated does not even begin to say whether one causes the other.'
That 2021 paper that Miller sees as the culmination of her life's work? It was based on surveys of 147 diagnosed MCAS patients from Afrin's clinic. Of that group, 59 percent—or 87 people—met the criteria for chemical intolerance. It's intriguing data but by no means conclusive. Nobody has yet taken a cohort of TILT-ed patients and done lab testing to investigate whether they have MCAS. 'In my opinion, that still needs to be done,' Afrin says. 'Different doctors have different styles—and Claudia, she's pretty convinced that we have enough associative evidence that it's a slam-dunk case. But TILT is just one of a zillion different diseases that MCAS is capable of driving.' And who to fund that research? TILT-ed patients would need to be well enough to travel to a clinic, where MCAS testing then costs thousands of dollars.
Then there's the string of bodies left in Miller's wake: An investigator on her UT team stopped speaking to her after she disapproved of some of his research and sent him a cease-and-desist letter for using her survey methodology. Another former staff member, Tatjana Walker, is now executive director of the Hoffman Foundation. The relationship is respectful but strained. When I told Miller that I was arranging to meet Walker, who also lives in San Antonio, she insisted that I could simply call Walker instead. The next day, Miller sent an email to me, Walker, several members of the foundation's scientific advisory board, and Ashford. In it, she tried to set up a meeting between Walker and me—at Miller's condo.
I arranged a separate chat with Walker over breakfast. Miller came up quickly. 'She's got a really strong vision of what she thinks the phenomenon is,' Walker said. 'And I would not be at all surprised to find out that she's correct.' As the saying goes, absence of evidence is not evidence of absence. 'But, in science, we try to take a step back and look at the bigger landscape.' She added that the foundation funds work about multiple chemical sensitivity because that's the most generally understood term. 'Claudia's invested a ton of time, a lot of thought, and, in many ways, her life,' she said. 'That's it: She's not the only person who has a thought about it.'
In Miller's second Don Quixote art piece, the protagonist lies on his deathbed, looking back on his life. Soldiers in the foreground, a windmill in the distance. At this point in the novel, Don Quixote has given up his fantasies. He advises his beloved niece to never marry a man like him.
The Don Quixote art in Miller's office. Photograph: Amber Gomez
I still hoped that Miller's work might bring my own family answers. About 14 years ago, my mom moved to a coastal town in Mexico. I called her up to discuss what I'd learned. As it turned out, she'd become familiar with mast cells several decades before. And? 'When I got blood work done, it didn't show high levels of mast cell activation,' she said. She'd tried a few commonly prescribed mast cell stabilizers, just in case. They didn't work. My heart sank. Maybe, she added, the tests have changed since then. I told her it could take multiple tests to pin down an MCAS diagnosis and that Afrin said that MCAS patients often need to experiment with a cocktail of meds to find a combination that works. 'I would try it again,' my mom said, kindly.
Whatever the case, since moving to Mexico, her health has improved. This aligns with the prevailing treatment for those with chemical intolerance: Avoid your triggers. My mom suspects that living in a foggy part of the San Francisco Bay Area with a lot of mold might have contributed to being TILT-ed. Where she lives now, it's dry, and many buildings are open-air. She still gets sick and can't tolerate fragrances and certain foods. But she's able to go for walks on the beach and run errands. She has more energy at 70 than she did throughout much of my childhood. She says stress reduction was one of the best things for her—and accepting that she might always feel adrift. 'I had to stop freaking out,' she said. (Not surprisingly, stress can also exacerbate MCAS flare-ups.)
Today, chemical intolerance is an accepted medical diagnosis in Japan and a recognized disability in Canada. It's unclear what a path forward might look like in the United States, though the Hoffman Foundation recently put out a request for proposals, which mentioned interest in expanding on mast cell theories and TILT. Miller is ready for everyone else to come around. 'I'm not saying I deserve a Nobel Prize,' she tells me. 'But it's at that level.' Her husband chimes in: 'Basically a new theory of disease. She thinks big, but the rest of the world doesn't think that way.'
Miller's symptoms have improved, which she attributes to stabilizing her mast cells with antihistamines and cromolyn. She also takes pre- and probiotics, plus pancreatic enzymes, to aid her digestion. Still, she can't drive—she has neuropathy, which she believes stemmed from her pesticide exposure. At the end of our day at the botanical garden, her husband gets behind the wheel of their SUV. Miller rides in back beside a roaring air filter, which she says prevents her from getting sleepy from a buildup of fumes. But she's exhausted anyway, and the noise drowns out her voice, which is thinner than ever. 'The question is, how do you get any of this into medical training?' Miller asks. Her eyelids droop behind her glasses.
There may not be an answer in her lifetime; I hope there will be one in mine. Walker told me that, back when she was working with Miller, 'one of Claudia's favorite expressions was: Science advances one funeral at a time.' It's much harder to let go of your own ideas than it is to pick up the thread of someone else's. Though, who knows, maybe that's what progress requires, like Don Quixote surrendering his illusions on his deathbed. It made me think back to a night in San Antonio when I went out to dinner with Miller and her husband. They paused by a tall water fountain in the restaurant's courtyard. Miller stepped close and tossed a penny underhand to make a wish. The coin winked in the air and then fell to the ground. Miller wasn't concerned: 'Some lucky person will find it exactly perfect.'
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Bridging Glycobiology and the Aging Brain: A Tale of Two Labs The study's inception came during Shi's PhD studies at Stanford University while she was jointly advised in the labs of Carolyn Bertozzi, PhD, a Nobel laureate and professor of chemical and systems biology at Stanford, and Tony Wyss-Coray, PhD, professor of neurology at Stanford. Tony Wyss-Coray, PhD 'I was really interested in trying to understand small chemical modification to proteins like glycans, and I found an interest in studying brain aging. We came up with fusing these two fields: glycobiology from Carolyn Bertozzi's lab and neurology from Tony Wyss-Coray's lab,' said Shi. Both Bertozzi and Wyss-Coray served as principal investigators of the study and are authors of the paper. Shi and the research team investigated a handful of older papers that had begun to investigate the endothelial glycocalyx in the brain. They noticed the researchers who authored those papers didn't follow up on their results — they'd stained glycocalyx sugars but didn't examine what these sugars really did. Realizing the field was understudied, Shi saw an opportunity to characterize the structural changes in the glycocalyx in age-related diseases. The team used a specialized staining tool — a product of Bertozzi's expertise in mucins — derived from a bacterial enzyme (StcE) to visualize mucin-domain glycoproteins lining the brain's blood vessels. '[Carolyn] had made this tool that allowed us to measure mucins…a very ingenious tool,' explained Wyss-Coray. 'It's an enzyme that bacteria make to cleave off mucins in the gut so they can infect. Carolyn used this [StcE] enzyme and introduced a mutation so it's no longer active but still binds to the mucins. That tool allowed us to visualize the mucins. We had a new tool that nobody could even imagine one could use.' This tool revealed a strong, continuous layer of these proteins in young mice that was significantly reduced and patchier in aged mice, a change that appeared specific to the brain. They then injected an active, 'cutting' version of the enzyme into young mice, which caused a significant breakdown of this entire protective glycocalyx layer. Clearly seeing this degradation on electron micrograph images served as the study's 'eureka' moment. 'I distinctly remember getting our first electron microscopy images back, those big pictures of the blood vessels showing degradation with age, and that was really striking,' said Shi. 'But we also did many orthogonal approaches to make sure it's really robust as a finding. Flow cytometry…transcriptional analysis…all of them pointed towards the same direction.' Restoring the Sugar Shield BBB's integrity relies on specialized endothelial cells with tight junctions and controlled transport systems. But the levels of two key sugar-building enzymes, C1GALT1 and B3GNT3, were significantly lower in the brain's blood vessels of old mice than in those of young mice. This decrease in the 'builder' enzymes directly correlated with the reduced amount of the final mucin 'sugar coat' that was present. Remarkably, the team successfully fixed this degeneration using adeno-associated viruses (AAVs) to overexpress these enzymes, which restored core 1 mucin-type O-glycans of the glycocalyx to the brain endothelium. This intervention not only improved the barrier's function but also led to a reduction in neuroinflammation and cognitive deficits in the animals. 'We're overexpressing these sugar molecules in the vasculature, which reduces leakiness, and then we showed that it reduces neuroinflammation, and then has these wonderful improvements in cognitive function,' explained Shi. The successful reversal of BBB leakiness and its cognitive consequences in this study's preclinical model suggests that strategies aimed at restoring the integrity of the brain's 'sugar shield' could be a potent strategy to combat the age-related breakdown of the BBB and mitigate diseases, though human trials would need to utilize other methods than viral vectors. Where This Takes Us While viral vector gene therapy proved effective in restoring the integrity of the glycocalyx, the exact mechanisms underlying its success require further explication. Restoring the glycocalyx can protect the brain by limiting the influx of neurotoxic circulatory factors like albumin and fibrinogen. However, the enzymes used in the therapy influence a wide range of proteins and glycan structures. A deeper understanding of all the molecular pathways affected may be warranted to fully grasp the processes of brain aging and rejuvenation. 'We do want to work on better understanding this pathway, to see where in the pathway we should really be targeting and see if there are small molecules that would be more therapeutically practical,' said Shi. Added Wyss-Coray, 'I think there's much more research that could be done. Do [mucins] have something to do with preventing pathogens from getting into the brain, more so than into another organ, once they make it into circulation? Do we have microorganisms that can enter the brain more easily? Another direction is to go find out where these sugars stick to.' The hope is this underappreciated class of mucin proteins can one day soon serve as a powerful new therapeutic target, opening a new frontier in the quest to combat age-related cognitive decline by focusing on rebuilding the brain's own protective shield. 'I think this is fantastic in the field,' said Wang. 'It really is a very fundamental study that shows how this mucin-type O-glycosylation in the vasculature is functionally very important....I think the [AVV therapy] is really important. It's possible [translational therapy on humans] can move quickly because AAV for the gene therapies are relatively common.'


CNN
17 minutes ago
- CNN
Mosquitoes bite! 5 tips for making yourself less attractive to them
EDITOR'S NOTE: The podcast Chasing Life With Dr. Sanjay Gupta explores the medical science behind some of life's mysteries big and small. You can listen to episodes here. (CNN) — For summertime beachgoers, the threat of sharks may loom large, but nature's deadliest predator is actually much smaller. The tiny mosquito is not only a warm-weather nuisance but also wears the crown for 'No. 1 killer of humanity across our existence,' according to historian Dr. Timothy C. Winegard. The predatory insect takes more than 1 million lives each year by transmitting lethal diseases. Sharks, meanwhile, are estimated to have a kill streak orders of magnitude smaller, at fewer than 10 people per year. Where humans go, mosquitoes have followed. Their itchy bites and the disease-causing pathogens they carry are infamous, and the insects are also responsible for driving many of humanity's most essential turning points throughout history, said Winegard, author of 'The Mosquito: A Human History of Our Deadliest Predator.' 'Malaria and yellow fever (have shaped) our historical journey from our hominid ancestral evolution … right to present day,' Winegard told CNN Chief Medical Correspondent Dr. Sanjay Gupta recently on his podcast, Chasing Life. Winegard, an associate professor of history at Colorado Mesa University, got the initial idea for his best-selling book from his dad's interest in malaria. The wee pest didn't intrigue Winegard too much at first. 'I kind of disparaged him and said, 'Sure, dad, I'll write a book on mosquitoes,'' he recalled. But once Winegard began going down the rabbit hole of mosquito-borne pathogens' impact on humanity — including, but not limited to malaria, Zika virus, dengue fever, yellow fever, chikungunya and West Nile virus — he couldn't stop. The mosquito's impact on history is still deeply felt in the present. More than half a million people die of malaria alone each year, and disease-heavy regions have suffered financially as a result. 'Northern Hemisphere countries don't have endemic malaria, (so) they're able to develop more affluent economies because they're not continuously suffering from malaria,' Winegard said. You can listen to the full episode here. Humans have been battling mosquitoes for millennia, and amid the season's summer peak in the Northern Hemisphere, Winegard offered some insight into how you can keep them away this summer. 'Eighty-five percent of what makes you alluring or less alluring to mosquitoes is prewired in your genetic circuit board,' according to Winegard. However, there are a few ways you can manage mosquitoes. He has these five tips. Booze makes it easier for mosquitoes to see you, Winegard said. Mosquitoes hunt by sight, but they don't see the world like people do. The predatory insects employ thermal, or infrared, vision. 'They see heat signatures,' Winegard noted. 'Consuming alcohol raises your body temperature,' he explained over email, 'which make(s) you an identifiable heat signature for your soon-to-be tormentor.' So, maybe reach for a refreshing glass of water or lemonade instead of that beer. In addition to using heat-based vision, mosquitoes hunt down humans primarily through smell. Winegard said mosquitoes 'can smell carbon dioxide from over 200 feet (60 meters) away.' 'So if you're exercising or breathing heavily, they'll smell that and be attracted to it,' Winegard told Gupta. And just like alcohol, high CO2 emissions make detecting heat signatures easier for mosquitoes, so Winegard recommends keeping yourself as cool as possible. This applies to your wardrobe, too. 'Dark clothes retain relatively more heat,' he said, so it's best to opt for lighter-colored, long-sleeved attire to keep mosquitoes at bay. Applying insect repellent is the gold standard for mosquito management, but if you're not careful when applying it, you can leave yourself vulnerable to bites. 'I know people who lather themselves in it, but they miss this little spot on the back of their calf and she'll find the chink in our armor,' Winegard told Gupta, referring to the female mosquito, who is the bloodsucking hunter. Mosquito repellent isn't like perfume, in which a few spritzes can cover your whole body. If you're spraying, make sure to be thorough. 'DEET (a chemical repellent) is still the gold standard, while oil of lemon eucalyptus is a plant-derived option,' Winegard said. For an added boost of security, he noted some clothes come pretreated with a mosquito-targeted insecticide called permethrin. Pool days and cool drinks outdoors offer a respite from the heat for humans, but they are equally as attractive to mosquitoes. Female mosquitoes lay their eggs in still water — and they don't need much. 'From a pond or stream to a minuscule collection in the bottom of an old container, used tire, or backyard toy — even a bottle cap full — any will suffice,' Winegard said via email. Even waterlogged soil is enough for mom-to-be mosquitoes to lay their eggs in, he added. Winegard recommended eliminating standing water around your home and yard to keep potential mosquito breeding grounds to a minimum. Another way to fight the swarms this summer is to consider skipping a shower or two. 'It's better to be stinky!' Winegard said. 'Being pungently rancid is a good thing, for it increases bacterial levels on the skin, which makes you less alluring to mosquitoes.' While this may offend others, Winegard says to skip the scented products: Deodorants, soaps and other applied fragrances are all enticing to mosquitoes. The one exception is your feet. 'Clean your feet,' he told Gupta. 'The bacteria on our feet, which is the same one that ripens a lot of cheeses, is an aphrodisiac to mosquitoes.' Winegard noted that this is the reason many of us get bitten around our ankles and feet. 'So, wash your feet!' he urged. Mosquitoes don't care about most personal characteristics you can objectively see. 'There is absolutely no truth to the persistent myths that mosquitoes fancy females over males, that they prefer blondes and redheads over those with darker hair, or that the darker or more leathery your skin, the safer you are from her bite,' Winegard said. But he noted that 'she does play favorites and feasts on some more than others.' What might entice a mosquito? 'Blood type O seems to be the vintage of choice over types A and B or their blend,' he said. 'People with blood type O get bitten twice as often as those with type A, with type B falling somewhere in between.' The creators of the 1998 movie 'A Bug's Life,' he noted, must have 'done their homework when portraying a tipsy mosquito ordering a 'Bloody Mary, O-positive.'' Maybe it's a mosquito's world, Winegard suggests, and people are just living in it. We hope these five tips help you keep mosquitoes at bay. Listen to the full episode here. And join us next week for a new episode of the Chasing Life podcast.

Wall Street Journal
17 minutes ago
- Wall Street Journal
GE HealthCare Raises 2025 Outlook After Earlier Reduction
GE HealthCare GEHC -0.03%decrease; red down pointing triangle raised its outlook for the year after trimming its forecast earlier in the year, reflecting greater certainty around tariffs. The maker of magnetic-resonance imaging scanners and other health-care machines now expects organic revenue growth of about 3% year over year compared to a previous forecast of growth between 2% and 3%. It also forecast adjusted earnings per-share in the range of $4.43 to $4.63, which includes around 45 cents in impacts from tariffs, and free cash flow of at least $1.4 billion.